BDNF signaling in context: From synaptic regulation to psychiatric disorders

Cell, Год журнала: 2021, Номер 185(1), С. 62 - 76

Опубликована: Дек. 27, 2021

Язык: Английский

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Brain-Derived Neurotrophic Factor Signaling in Depression and Antidepressant Action

Biological Psychiatry, Год журнала: 2021, Номер 90(2), С. 128 - 136

Опубликована: Май 14, 2021

Neurotrophic factors, particularly BDNF (brain-derived neurotrophic factor), have been associated with depression and antidepressant drug action. A variety of preclinical clinical studies implicated impaired signaling through its receptor TrkB (neurotrophic tyrosine kinase 2) in the pathophysiology mood disorders, but many initial findings not fully supported by more recent meta-analyses, both basic research is needed. In contrast, increased expression has repeatedly mechanisms typical rapid-acting drugs, started to elucidate which antidepressants regulate signaling. a critical regulator various types neuronal plasticities brain, plasticity increasingly connected Although some equivocal data exist, hypothesis connection between factors disorders action recently further strengthened converging evidence from reviewed here.

Язык: Английский

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The promises and perils of psychedelic pharmacology for psychiatry

Nature Reviews Drug Discovery, Год журнала: 2022, Номер 21(6), С. 463 - 473

Опубликована: Март 17, 2022

Язык: Английский

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The role of dissociation in ketamine’s antidepressant effects

Nature Communications, Год журнала: 2020, Номер 11(1)

Опубликована: Дек. 22, 2020

Abstract Ketamine produces immediate antidepressant effects and has inspired research into next-generation treatments. also short term dissociative effects, in which individuals report altered consciousness perceptions of themselves their environment. However, whether ketamine’s side are necessary for its remains unclear. This perspective examines the relationship between acute longer-lasting response to ketamine other N-methyl-D-aspartate (NMDA) receptor antagonists. Presently, literature does not support conclusion that dissociation is ketamine. further work needed explore at molecular, biomarker, psychological levels.

Язык: Английский

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Ketamine and rapid antidepressant action: new treatments and novel synaptic signaling mechanisms

Neuropsychopharmacology, Год журнала: 2023, Номер 49(1), С. 41 - 50

Опубликована: Июль 24, 2023

Abstract Ketamine is an open channel blocker of ionotropic glutamatergic N -Methyl- D -Aspartate (NMDA) receptors. The discovery its rapid antidepressant effects in patients with depression and treatment-resistant fostered novel effective treatments for mood disorders. This not only provided new insight into the neurobiology disorders but also uncovered fundamental synaptic plasticity mechanisms that underlie treatment. In this review, we discuss key clinical aspects ketamine’s effect as a rapidly acting antidepressant, circuit underlying action, well how these perspectives practice synapse biology form road map future studies aimed at more neuropsychiatric

Язык: Английский

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Shared and Distinct Brain Regions Targeted for Immediate Early Gene Expression by Ketamine and Psilocybin

ACS Chemical Neuroscience, Год журнала: 2023, Номер 14(3), С. 468 - 480

Опубликована: Янв. 11, 2023

Psilocybin is a psychedelic with therapeutic potential. While there growing evidence that psilocybin exerts its beneficial effects through enhancing neural plasticity, the exact brain regions involved are not completely understood. Determining impact of on plasticity-related gene expression throughout can broaden our understanding circuits in psychedelic-evoked plasticity. In this study, whole-brain serial two-photon microscopy and light sheet were employed to map immediate early gene, c-Fos, male female mice. The drug-induced c-Fos following administration was compared subanesthetic ketamine saline control. produced acutely comparable elevations numerous regions, including anterior cingulate cortex, locus coeruleus, primary visual central basolateral amygdala, medial lateral habenula, claustrum. Select exhibited drug-preferential differences, such as dorsal raphe insular cortex for CA1 subfield hippocampus ketamine. To gain insights into contributions receptors cell types, maps related brain-wide situ hybridization data. transcript analyses showed endogenous levels

Язык: Английский

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Biochemical Mechanisms Underlying Psychedelic-Induced Neuroplasticity

Biochemistry, Год журнала: 2022, Номер 61(3), С. 127 - 136

Опубликована: Янв. 21, 2022

In addition to producing profound subjective effects following acute administration, psychedelic compounds can induce beneficial behavioral changes relevant the treatment of neuropsychiatric disorders that last long after have been cleared from body. One hypothesis with potential explain remarkable enduring psychedelics is related their abilities promote structural and functional neuroplasticity in prefrontal cortex (PFC). A hallmark many stress-related diseases, including depression, post-traumatic stress disorder (PTSD), addiction, atrophy neurons PFC. Psychedelics appear be particularly effective catalysts for growth these key neurons, ultimately leading restoration synaptic connectivity this critical brain region. Furthermore, evidence suggests hallucinogenic are not directly linked ability neuroplasticity. If we develop improved alternatives treating must fully characterize molecular mechanisms give rise psychedelic-induced Here, I review our current understanding biochemical signaling pathways activated by neuroplasticity-promoting molecules, an emphasis on unanswered questions.

Язык: Английский

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NMDA Receptor Activation-Dependent Antidepressant-Relevant Behavioral and Synaptic Actions of Ketamine

Journal of Neuroscience, Год журнала: 2023, Номер 43(6), С. 1038 - 1050

Опубликована: Янв. 3, 2023

Ketamine is a well-characterized NMDA receptor (NMDAR) antagonist, although the relevance of this pharmacology to its rapid (within hours administration) antidepressant actions, which depend on mechanisms convergent with strengthening excitatory synapses, unclear. Activation synaptic NMDARs necessary for induction canonical long-term potentiation (LTP) leading sustained expression increased strength. We tested hypothesis that effects requires NMDAR activation, by using behavioral pharmacology, western blot quantification hippocampal synaptoneurosomal protein levels, and

Язык: Английский

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Ketamine: Mechanisms and Relevance to Treatment of Depression

Annual Review of Medicine, Год журнала: 2023, Номер 75(1), С. 129 - 143

Опубликована: Сен. 20, 2023

Major depressive disorder (MDD) is a leading cause of suicide in the world. Monoamine-based antidepressant drugs are primary line treatment for this mental disorder, although delayed response and incomplete efficacy some patients highlight need improved therapeutic approaches. Over past two decades, ketamine has shown rapid onset with sustained (up to several days) effects whose MDD not responded conventional drugs. Recent preclinical studies have started elucidate underlying mechanisms ketamine's properties. Herein, we describe compare recent clinical findings provide broad perspective relevant action ketamine.

Язык: Английский

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A Dendrite-Focused Framework for Understanding the Actions of Ketamine and Psychedelics

Trends in Neurosciences, Год журнала: 2020, Номер 44(4), С. 260 - 275

Опубликована: Дек. 21, 2020

Язык: Английский

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